This document discusses different types of vasculitis and disorders of blood vessel hyperreactivity. It describes how vasculitis can be caused by immune-mediated inflammation, direct infection, or physical/chemical injury. The main immunologic mechanisms are immune complex deposition, antineutrophil cytoplasmic antibodies, anti-endothelial cell antibodies, and autoreactive T cells. It also discusses Raynaud phenomenon and myocardial vessel vasospasm as examples of disorders involving exaggerated vasoconstriction.

1. Pathophysiology
Cardiovascular system (part 3)
Lecture 6
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‫خالد‬

2. Vasculitis
• is a general term for vessel wall inflammation.
• The clinical manifestations largely depend on the specific affected blood
vessels.
• Vasculitis mostly affects small vessels (arterioles, capillaries, and venules).
• However large vessels (e.g., large or medium-sized muscular arteries), can
be affected

3. The most common pathogenic mechanisms of vasculitis
Immune-mediated inflammation
Direct vascular invasion by infectious
pathogens.

4. Infections also can indirectly precipitate
immune-mediated vasculitis
By generating
immune complexes
Triggering cross-
reactivity.

5. Other causes of vasculitis
• Physical and chemical injury, including that due to
radiation, mechanical trauma, and toxins.

6. • It is critical to distinguish between Infectious and immunologic
mechanisms because immunosuppressive therapy is appropriate
for immune-mediated vasculitis But could Exacerbate infectious
vasculitis

7. Noninfectious Vasculitis
The main immunologic mechanisms underlying noninfectious vasculitis
are
• Immune complex deposition
• Antineutrophil cytoplasmic antibodies
• Anti-endothelial cell antibodies
• Autoreactive T cells

8. 1-immune Complex–Associated Vasculitis.
• This form of vasculitis is seen in immunologic disorders such as systemic lupus
erythematosus that are associated with autoantibody production.
• Immune complex deposition is implicated in the following vasculitides:
 Drug hypersensitivity vasculitis.
 Vasculitis secondary to infections.

9. Drug hypersensitivity vasculitis.
• In some cases, drugs (e.g., penicillin) act as haptens by binding to host proteins;
• Other agents are themselves foreign proteins (e.g., streptokinase).
• The clinical manifestations can be mild and self-limiting, or severe and even
fatal;
• It is always important to consider drug hypersensitivity as a cause of vasculitis
since discontinuation of the offending agent usually leads to resolution.

10. Vasculitis secondary to infections.
• Antibodies to microbial constituents can form immune complexes that
circulate and deposit in vascular lesions.
• In up to 30% of patients with polyarteritis nodosa, the vasculitis is
attributable to immune complexes composed of hepatitis B surface
antigen (HBsAg) and anti-HBsAgs antibody.

11. 2- Anti-Neutrophil Cytoplasmic Antibodies.
• Many patients with vasculitis have circulating antibodies that react with neutrophil
cytoplasmic antigens, so-called anti-neutrophil cytoplasmic antibodies (ANCAs).
• Anti-neutrophil cytoplasmic antibodies are very useful diagnostic markers

12. The two most important ANCAs are
Antiproteinase-3 (PR3-ANCA),
Anti-myeloperoxidase (MPO-ANCA),

13. Infectious Vasculitis
• Localized arteritis may be caused by the direct invasion of
arteries by infectious agents, usually bacteria or fungi.
• Vascular infections can weaken arterial walls and result in
aneurysms or can induce thrombosis and infarction.

14. Disorders of blood vessel
hyperreactivity
Raynaud
Phenomenon
Myocardial
Vessel
Vasospasm

15. Raynaud Phenomenon
• Raynaud phenomenon results from exaggerated vasoconstriction of
arteries and arterioles in the extremities, particularly the fingers and
toes, but also sometimes the nose, earlobes, or lips.
• The restricted blood flow induces paroxysmal pallor or cyanosis.
Produce red-white-and-blue” color changes.

19. Raynaud phenomenon can be
A primary Secondary to other
disorders.

20. Primary Raynaud phenomenon (previously called Raynaud disease)
Is caused by exaggerated central and local vasomotor
responses to cold or emotion.
It affects 3%-5% of the general population and mostly
occurs in young women.
The course usually is benign, but in chronic cases, atrophy
of the skin, subcutaneous tissues, and muscles may occur.

21. Secondary Raynaud phenomenon
• refers to vascular insufficiency due to other arterial
diseases including systemic lupus erythematosus,
scleroderma, or even atherosclerosis

22. Myocardial Vessel Vasospasm
• Excessive constriction of myocardial arteries or arterioles may cause ischemia and
persistent vasospasm can even lead to tissue infarction.
• It is aggravated by endogenous mediators (epinephrine) or exogenous (cocaine or
phenylephrine).
• In some susceptible persons, extreme psychological stress with the concomitant release
of catecholamines can lead to pathologic vasospasm.

23. • When vasospasm of cardiac arterial or arteriolar beds (so-called cardiac Raynaud)
is of sufficient duration (20 to 30 minutes), a myocardial infarction occurs.
• The outcome can be
1. Sudden cardiac death (probably caused by a fatal arrhythmia).
2. An ischemic dilated cardiomyopathy—so-called Takotsubo cardiomyopathy
(also called “broken heart syndrome,” because of the association with emotional
duress).